SAN DIEGO, Jul 26, 2004 /PRNewswire-FirstCall via COMTEX/ -- Arena Pharmaceuticals, Inc.
(Nasdaq: ARNA) announced today that it has initiated a Phase 1b clinical trial
of APD356, its 5-HT2C selective, lead anti-obesity compound. The purpose of
this Phase 1b study is to evaluate safety at steady state drug levels during
14-day repeated daily dosing. This double-blind, placebo-controlled,
dose-escalation, multiple-dose study is enrolling healthy, overweight and
obese volunteers, and follows the company's successful completion of its
Phase 1a, single-dose study. The trial is being performed at a site in the
United States.

The Phase 1b clinical trial should be completed in the second half of this
year. If the results support further testing, the company anticipates
launching a Phase 2 clinical trial in overweight and obese patients by the end
of the year.

About APD356

Obesity and metabolic syndrome are conditions that affect tens of millions
of adults and children and pose a serious long-term threat to their health and
welfare. In the previous Phase 1a single-dose clinical trial, evidence of a
pharmacological effect on food intake was seen with a single 10 mg dose of
APD356. The 10 mg dose was well tolerated, and produced peak drug levels in
blood that are some 20-fold greater than the in vitro EC50 for the 5-HT2C
receptor, the pharmacologic target for APD356. Dose escalation was stopped
after the 40 mg dose due to CNS side effects consistent with a high dose of a
serotonergic drug. APD356 was pharmacokinetically well behaved, with minimal
inter-subject variability, excellent dose proportionality and a half-life
suitable to once daily dosing. Food did not affect the absorption of APD356,
which suggests that it can be taken before or after a meal.

In animal models of obesity, APD356 reduced body weight and food intake,
which, Arena believes, is due to the compound's ability to regulate satiety
and perhaps metabolism. Arena's in vivo experiments showed that APD356
selectively reduced fat mass in obese animals, while leaving lean body mass
unchanged, a very desirable outcome. Stimulation of the 5-HT2C receptor is
thought to play an important role in weight loss. APD356 has approximately
100-fold selectivity in vitro for the 5-HT2C receptor relative to the 5-HT2B
receptor, the receptor primarily implicated in the cardiac valvulopathy
observed with non-selective serotonergic drugs. In addition, APD356 has
approximately 15-fold selectivity in vitro for the 5-HT2C receptor versus the
5-HT2A receptor, the central nervous system (CNS) receptor thought to be
primarily responsible for most of the CNS adverse effects of non-selective
serotonergic agents. It is hypothesized that its selectivity will allow
APD356 to be dosed at a level that will induce clinically relevant weight loss
while avoiding the cardiovascular side effects observed with non-selective
serotonergic agents.

About Arena

Arena is a biopharmaceutical company focusing on the discovery,
development and commercialization of drugs in four major therapeutic areas:
metabolic, cardiovascular, inflammatory and central nervous system diseases.
Arena is developing a broad pipeline of compounds that act on an important
class of drug targets called G protein-coupled receptors, or GPCRs, and that
are being developed using Arena's proprietary technologies, including CART
(Constitutively Activated Receptor Technology) and Melanophore. Arena also
has research collaborations with Merck, Fujisawa, Taisho and TaiGen for
products in a number of different indications. For additional information
about Arena, visit their website at http://www.arenapharm.com.

Forward-Looking Statements

Certain statements in this press release are forward-looking statements
that involve a number of risks and uncertainties. Such forward-looking
statements include statements about when, whether and how Arena expects to
continue further clinical testing on APD356 and Arena's strategy,
technologies, preclinical and clinical programs, ability to identify and
develop drugs, future achievements, goals and expectations, as well as other
statements that are not historical facts, including statements that are
preceded by the word "will" or similar words. For such statements, Arena
claims the protection of the Private Securities Litigation Reform Act of 1995.
Actual events or results may differ materially from Arena's expectations.
Factors that could cause actual results to differ materially from the
forward-looking statements include, but are not limited to, the timing,
success and cost of Arena's research, out-licensing endeavors and clinical
studies, Arena's ability to obtain additional financing from collaborators or
investors, and the timing and receipt of payments and fees, if any, from
Arena's collaborators. Additional factors that could cause actual results to
differ materially from those stated or implied by Arena's forward-looking
statements are disclosed in Arena's SEC reports, including Arena's most recent
quarterly report on Form 10-Q and its recently filed registration statement on
Form S-3. These forward-looking statements represent Arena's judgment as of
the date of this release. Arena disclaims any intent or obligation to update
these forward-looking statements.

Arena Pharmaceuticals® and Arena® are registered service marks of the
company. CART is an unregistered service mark of the company.